Antibodies to DNA and to polyadenylic acid (poly A) occur spontaneously in systemic lupus erythematosus (SLE) and in NZB/NZW Fl (B/W) mice, an animal model for autoimmunity. In the mice, this antibody response is regulated by lymphoid organs (particularly the thymus) and by sex hormones. The thymus exerts a suppressor influence in male mice. Androgens suppress antibodies to nucleic acids and prolong survival, whereas estrogens promote autoimmunity and decrease survival. Immunologic regulation of the antibody response to DNA and poly A will be studied in an adoptive transfer system and in an in vitro spleen cell culture system which synthesizes these autoantibodies. The potential therapeutic use of androgen will be explored in B/W mice with established disease. The ability of lipopolysaccharide (LPS) to induce antibodies to nucleic acids also be investigated.